ivivc correlation

1. COMPUTER AIDED
DRUG DEVELOPMENT
PRESENTED BY
C.HARISH
(1st m-
pharm)

2. DEFINATION
• In vitro dissolution: It’s a process of release of drug from
dosage form as measured in an in vitro dissolution
apparatus
• In vivo dissolution: process of dissolution of drug in the
GI tract.
• Correlation: relationship between in vitro dissolution rate
and
in vivo absorption rate as used in bio-equivalence guidance
• IVIVC has been defined as “a predictive mathematical
model
describing the relationship between an in-vitro property of a
dosage form and an in-vivo response”

3. Levels of correlation
• Level A Correlation
• Level B Correlation
• Level C Correlation
• Multiple Level C Correlation

4. Level A correlation
 It is estimated by two step method,
deconvolution followed by comparison
of fraction of drug absorbed to the
fraction of drug dissolved.
 Defines a direct relationship between in
vivo data such that measurement of in
vitro dissolution rate alone is sufficient
to determine the biopharmaceutical rate
of the dosage form.
 An in vitro dissolution curve can serve
as a surrogate for in vivo performance
Figure 5: Correlation between percent
theophylline dissolved in vitro and
percent theophylline absorbed after
administration of extended release
product

5. Level B correlation
 Level B correlation utilizes the
principles of statistical moment
analysis.
 Mean in vitro dissolution time
(MDTvitro) of the product is compared
to mean in vivo residence time
(MRT).
 MRT may be calculated as the ratio of
the area under the first moment curve
(AUMC) to the AUC, where AUMC
is the area under the curve observed
for the product of time and
concentration versus time.

6. Level C correlation
 Level C correlation represents a single
point correlation.
 One dissolution time point (t50%, t90%,
etc.) is compared to one mean
pharmacokinetic parameter such as
AUC, tmax or Cmax.
 Weakest level of correlation as partial
relationship between absorption and
dissolution is established

7. Multiple level C correlations
 Multiple Level C correlation relates one or
several pharmacokinetic parameters of interest
(Cmax, AUC, or anyother suitable parameters)
to the amount of drug dissolved as several
time points of the dissolution profile.
Its correlation is more meaningful than that
of Level C asseveral time points are
considered.

8. BCS CLASSIFICATION

9. • Class1 drug : exhibit a high absorption no & high dissolution no &
rate limiting step is drug dissolution or gastric empting time.
• Eg. metoprolol
IVIVC IS EXPECTED
• Class-2 drug:-drugs under this class have low solubilityand high
permeability
Eg-phenytoin
Ivivc expected
• Class-3 drug:-drugs like permeability is rate controllingstep rapid
dissolution is particularly desirable in order tomaximize the contact time
between dissolve drug andabsorption mucosa.
Eg. cimetidine
Limited or no IvIvc expected
• Class 4 drug:- they have low solubility low permeabilityand
significant problem in oral dosage form.
Limited or no IvIvc expectedXPECTED

10. CONCEPT OF IVIVC
 The concept of IVIVC has been extensively discussed for
modified release dosage forms.
 This is because the dissolution behavior of of the drug from ER or
MR product is the rate limiting factor for absorption in GIT.
 This is why IVIVC are expected more generally for ER formulations
than with IR products especially when the latter releases the drug
rapidly (>80 % in < 20 minutes)
 But, it does not mean that IVIVC cannot be applied for IR products.
 In recent times, IVIVC used for parenterals, transdermals,
pulmonary formulations etc..

11. NEED OF IVIVC
 To minimize unnecessary human testing
 To Minimization of cost and time
 To set up bio pharmaceutically meaningful
invitro release specifications
 Decreased regulatory burdens